Field of the Invention
The invention in general pertains to osteoporosis and therapeutic interventions thereof in mammals. More specifically, the present invention pertains to the therapeutic potential of Calebin A for osteoporosis wherein calebin A in therapeutically effective amounts is shown to inhibit mammalian osteoclastogenesis by the suppression of the RANKL signaling pathway thereby evincing therapeutic potential for osteoporosis.
Description of the Prior Art
An estimated 61 million people aged 50 years or older in the United States would be prone to risk for fractures following osteoclast related bone diseases like osteoporosis or low bone mass by 2020 due to the non availability of widely implemented and effective treatment. According to the American Academy of Orthopedic Surgeons, the projected cost of osteoporosis care over the next 2 decades will be approximately $474 billion (Z. Jin, X. Li, Y. Wan, Mol. Endocrinol. 29 (2015) 172-186).
Bone metastasis is common sequelae of multiple myeloma or advanced breast, prostate, lung, colon, kidney, thyroid, and stomach carcinomas (R. E. Coleman, Cancer Treat. Rev. 27 (2001) 165-176 and R. E. Coleman, Clin. Cancer Res. Off. J. Am. Assoc). The involvement of a cytokine belonging to the tumour necrosis factor (TNF) family called receptor activator of nuclear factor (NF)-κB ligand (RANKL) in such metastasis has been reported in the art (T. Onishi, N. Hayashi, R. L. Theriault, G. N. Hortobagyi, N. T. Ueno, Nat. Rev. Clin. Oncol. 7 (2010) 641-651). RANKL has been demonstrated to possess osteoclastogenic activity, whereby RANKL directs the differentiation of bone monocytes to osteoclasts which promote bone resorption (D. L. Lacey, E. Timms, H. L. Tan, M. J. Kelley, C. R. Dunstan, T. Burgess, R. Elliott, A. Colombero, G. Elliott, S. Scully, H. Hsu, J. Sullivan, N. Hawkins, E. Davy, C. Capparelli, A. Eli, Y. X. Qian, S. Kaufman, I. Sarosi, V. Shalhoub, G. Senaldi, J. Guo, J. Delaney, W. J. Boyle, Cell 93 (1998) 165-176 and S. L. Teitelbaum, Science 289 (2000) 1504-1508).
Curcumin is also reported to suppress osteoclastogenesis (A. C. Bharti, Y. Takada, B. B. Aggarwal, J. Immunol. (2004) 172, 5940-5947). Other natural ingredients for managing osteoporosis and cancer induced osteoclastogenesis remain to be investigated. Calebin A as a natural ingredient is known in the art for its anti-cancer properties (Li Y et al, “Calebin-A induces apoptosis and modulates MAPK family activity in drug resistant human gastric cancer cells”, Eur J Pharmacol. 2008 Sep. 4; 591(1-3):252-258 and Aggarwal B B et al, “Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric”, Mol Nutr Food Res. 2013 September; 57(9):1529-42). The present invention investigates the ability of calebin A to suppress osteoclastogenesis in mammals.
It is the principle objective of the invention to disclose the therapeutic potential of calebin A for mammalian osteoporosis wherein calebin A is shown to inhibit both RANKL- and cancer-induced osteoclastogenesis.
The present invention fulfils the aforesaid objective and also provides related advantages.